Certain strange diseases are scary to think about. The news pages are dominated by tragedies caused by diseases like Ebola, Mad Cow Disease, or Progeria, but when it comes to everyday illnesses, there’s almost nothing more prevalent than redundancy depression. It takes the sparkle out of life, turns millions of people (about 15 percent of the population) into disabled individuals, and has the potential to become the second leading cause of medical disability worldwide within a decade. Many factors increase the risk of developing major depression, including variations in several genes, early childhood trauma, endocrine abnormalities and abnormal immune function. Stress is a common trigger. Recent research has shed light on the mechanisms by which stress may lead to major depression. New research reveals a portion of the specific biological mechanisms behind depression. The ability to anticipate, pursue and feel pleasure hinges on a neurotransmitter called dopamine in the nucleus accumbens region of the brain. University of Washington (University of Washington) Julia Lemos (Julia Lemos), Matthew Wanat (Matthew Wanat), Paul Phillips (Paul Phillips) and colleagues in the “Nature” (Nature) and “Nature Neuroscience” (Nature Neuroscience). Nature and Nature Neuroscience, explored the effects of stress on dopamine in rats. Instead of simply examining the rewarding properties of pleasurable things like sex or sweets, they looked at a more subtle form of pleasure. A novel object, say a ball, was placed in the rat’s cage. When the rats found the ball and explored it, feelings of mystery, confusion, and challenge emerged, leading to the release of a molecule in the nucleus ambiguus called CRF, which promotes dopamine release. If the unexpected novel object had been a cat, the working mechanism of the rat brain would have been very different. But getting the optimal number of challenges (what we call “stimuli”) makes rats feel good. CRF coordinates such a response: block CRF behavior with a drug, and then there is no more dopamine surge and the rats will no longer engage in probing behavior. Or, according to another experimental method, if CRF is sprayed into the nucleus accumbens every time a rat sneaks into a corner of the cage, then the rat will return to that spot repeatedly; i.e., CRF has a “reinforcing property”. But if the rats are exposed to heavy, constant stress for several days, everything is different: CRF no longer enhances dopamine release, and the rats avoid novel objects. In addition, CRF now has a disliking property: spray it into the nucleus ambiguus and now the rats won’t go to that corner of the cage. The authors point out that this is due to the action of the stress hormone “glucocorticoids”. Everything was reversed, and the stimuli that would normally provoke positive exploratory behavior and feelings of reward now provoked the opposite. It’s worth noting that the stress of those days caused the rats’ pleasure-deprived state to last for at least three months. As with all good research, more questions were raised: how did glucocorticoids cause these changes? Do the rats recover? Are some individuals resistant to these effects? Is it the same mechanism in humans? But at the same time, these findings have an important implication. Life throws nasty things at us; we all feel depressed from time to time, just not the depression kind of depression. And most people make a comeback, as the saying goes, proving that strong people get stronger in the face of adversity. So what about people who become clinically disabled because of major depression? Unfortunately, the reason, in the minds of many, is the simple fact that the illness is the result of a lack of gumption: “Come on, snap out of it!” There is a moral demeaning implicit in this. Therefore, when scientists reveal the specific biological mechanisms of depression, it is not only medically beneficial, but also beneficial in a sociological sense, because these studies can point to the fact that depression is an objective biological disorder. It is as objective as diabetes, and we don’t have the diabetic sitting up front and saying to him, “Stop indulging, you have to get over your obsession with insulin.”